A validated chiral liquid chromatographic method for the enantiomeric separation of Rivastigmine hydrogen tartarate, a cholinesterase inhibitor.

摘要

A new and accurate chiral liquid chromatographic method was developed for the enantiomeric resolution of Rivastigmine hydrogen tartarate, (-)S-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methylphenyl-carbamate hydrogen tartarate, a cholinesterase inhibitor in bulk drugs. The enantiomers of Rivastigmine hydrogen tartarate were baseline resolved on a Chiralcel OD-H (250mmx4.6mm, 5mum) column using a mobile phase system containing hexane: isopropanol: trifluoroacetic acid (80:20:0.2, v/v/v). The resolution between the enantiomers was not less than four and interestingly distomer was eluted prior to eutomer in the developed method. The presence of trifluoroacetic acid in the mobile phase has played an important role in enhancing chromatographic efficiency and resolution between the enantiomers. The developed method was extensively validated and proved to be robust. The limit of detection and limit of quantification of (R)-enantiomer were found to be 500 and 1500ng/ml, respectively for 10mul injection volume. Thepercentage recovery of (R)-enantiomer was ranged from 95.2 to 104.3 in bulk drug samples of Rivastigmine hydrogen tartarate. Rivastigmine hydrogen tartarate sample solution and mobile phase were found to be stable for at least 48h. The proposed method was found to be suitable and accurate for the quantitative determination of (R)-enantiomer in bulk drugs. Chiralcel OJ-H column can also be used as an alternative for the above purpose.